Menthylcarboxamides and Their Use as Cooling Agents

ABSTRACT

Described is a new cooling agent represented by Structure I and compositions with known coolers having cooling properties and the application of Structure I in foodstuffs and chewing gum:

FIELD OF INVENTION

The following invention relates to edible compositions having a unique,long lasting, cooling perception which provides the user with anenhanced perception of breath-freshening without bitterness. Thefollowing invention is useful in chewing gum compositions andconfectionary compositions which provide a long-lasting, breathfreshening perception without bitterness.

BACKGROUND OF THE INVENTION

Cooling agents are describes as chemical compounds providing cold orcool sensations when contacted with the human body, especially with themucus membranes of the mouth, nose and throat. Cooling compounds arewidely used in edible products, beverages, dentifrices, tobaccoproducts, mouthwashes and toiletries.

One class of cooling compounds which are very effective compoundscontaining an N-substituted p-menthane carboxamide moiety. Examples ofthese compounds are described in, for example, British Patents GB1,351,761-2 and U.S. Pat. No. 4,150,052.

Properties of those compounds are based on l-menthol, which is one ofthe most well-known physiological coolants, and which has been widelyused in several applications. L-menthol has an excellent coolingstrength and is relatively inexpensive.

It is well recognized that one of the purpose of chewing gum andconfectionery products is to enhance ones breath and provide a clean,cool, fresh feeling in the mouth. Unfortunately, most products are notable to maintain such perception for long periods of time, which is atime up to about thirty minutes.

The compound of the present invention may be used alone or incombination with additional compounds or composition which increasecooling and flavor impact and extend these taste effects over aprolonged period of time.

SUMMARY OF THE INVENTION

According to one embodiment of the invention the following Structure isdisclosed

In an additional embodiment the use of Structure I as a coolingcomposition is disclosed.

In yet a further embodiment of the invention, the combination ofStructure I with other compounds and compositions having coolingproperties is disclosed.

In still another embodiment a composition is provided containingStructure I.

In yet another embodiment of the invention a composition is providedcontaining the combination of Structure I with other compounds andcompositions having cooling properties.

In another embodiment of the invention an ingestible product for humansor animals which comprises a product base selected from the groupconsisting of baked goods, dairy products, fruit ices, confectioneryproducts, sugarless candies, jams, jellies, gelatins, puddings, animalfeeds, pressed confectionery tablets, hard-boiled candies, pectin-basedcandies, chewy candies, creme-centered candies, fondants, sugarlesshard-boiled candies, sugarless pectin-based candies, sugarless chewycandies, sugarless creme-centered candies, toothpastes, mouthwashes,breath fresheners, carbonated beverages, mineral waters, powderedbeverage mixes, other non-alcoholic beverages, cough drops, lozenges,cough mixtures, decongestants, anti-irritants, antacids,anti-indigestion preparations and oral analgesics, and an effectiveamount of a compound:

In accordance with a another embodiment of the present invention, achewing gum composition which is capable of providing long-lasting,breath freshening perception without bitterness comprises a gum base, asweetener and a cooling composition comprising N-substituted-p-menthanecarboxamide of the Structure I:

In further embodiments of the invention, a chewing gum composition whichis capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with monomenthyl glutarate is disclosed.

In a further embodiment of the invention, a chewing gum compositionwhich is capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with 2-isopropyl-N,2,3-trimethylbutyramid isdisclosed.

In yet a further embodiment of the invention, a chewing gum compositionwhich is capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with menthyl acetoacetate is disclosed.

In another embodiment of the invention, a chewing gum composition whichis capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with N-ethyl-p-menthanecarboxamide isdisclosed.

Another embodiment of the invention is directed to a process foraugmenting, enhancing or imparting a taste or cooling or refreshingeffect in or to a cosmetic, skin care product, lip gloss, hair careproduct, cologne, shaving balm, after-shave lotion, dairy product, fruitice preparation, confectionery, mouth and throat lozenges, coughmixtures, decongestants, antacids, oral analgesics or other medicinalproducts, chewing gum, candy (including hard candy and soft candy),fondants, toothpaste, mouthwashes, mineral water, alcoholic beverage,non-alcoholic beverage, powdered beverage, or other foodstuff comprisingthe step of adding to a cosmetic, skin care product, lip gloss, haircare product, cologne, shaving balm, after-shave lotion, dairy product,fruit ice preparation, confectionery, lozenges, cough mixtures,decongestants, antacids, oral analgesics or other medicinal product,chewing gum, candy, fondants, toothpaste, mouthwashes, mineral water,alcoholic beverage, non-alcoholic beverage, powdered beverage, or otherfoodstuff, a taste or cooling or refreshing effect augmenting, enhancingor imparting quantity and concentration of Structure I:

DETAILED DESCRIPTION OF THE INVENTION

Applicants have unexpectedly found that N-substituted-p-menthanecarboxamide represented by Structure I, when used by itself or incombination with another coolers such as, but not limited, menthol,menthone, monomenthyl glutarate, 2-isopropyl-N,2,3-trimethylbutyramide,N-ethyl-p-menthanecarboxamide, or menthyl acetoacetate results in anunexpected heightened cooling sensation in edible products.

In a further embodiment of the invention the combination of Structure Iwith monomenthyl glutarate is disclosed.

In still a further embodiment of the invention the combination ofStructure I with 2-isopropyl-N,2,3-trimethylbutyramid is disclosed.

In yet another embodiment of the invention the combination of StructureI with menthyl acetoacetate is disclosed.

In a further embodiment of the invention the combination of Structure Iwith N-ethyl-p-menthanecarboxamide is disclosed.

In accordance with a another embodiment of the present invention, achewing gum composition which is capable of providing long-lasting,breath freshening perception without bitterness comprises a gum base, asweetener and a cooling composition comprising N-substituted-p-menthanecarboxamide of the Structure I:

In further embodiments of the invention, a chewing gum composition whichis capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with monomenthyl glutarate is disclosed.

In a further embodiment of the invention, a chewing gum compositionwhich is capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with 2-isopropyl-N,2,3-trimethylbutyramid isdisclosed.

In yet a further embodiment of the invention, a chewing gum compositionwhich is capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with menthyl acetoacetate is disclosed.

In another embodiment of the invention, a chewing gum composition whichis capable of providing long-lasting, breath freshening perceptionwithout bitterness comprises a gum base, a sweetener and a coolingcomposition comprising N-substituted-p-menthane carboxamide of theStructure I in combination with N-ethyl-p-menthanecarboxamide isdisclosed.

In another embodiment of the invention an ingestible product for humansor animals which comprises a product base selected from the groupconsisting of baked goods, dairy products, fruit ices, confectioneryproducts, sugarless candies, jams, jellies, gelatins, puddings, animalfeeds, pressed confectionery tablets, hard-boiled candies, pectin-basedcandies, chewy candies, creme-centered candies, fondants, sugarlesshard-boiled candies, sugarless pectin-based candies, sugarless chewycandies, sugarless creme-centered candies, toothpastes, mouthwashes,breath fresheners, carbonated beverages, mineral waters, powderedbeverage mixes, other non-alcoholic beverages, cough drops, lozenges,cough mixtures, decongestants, anti-irritants, antacids,anti-indigestion preparations and oral analgesics, and an effectiveamount of a compound:

Another embodiment of the invention is directed to a process foraugmenting, enhancing or imparting a taste or cooling or refreshingeffect in or to a cosmetic, skin care product, lip gloss, hair careproduct, cologne, shaving balm, after-shave lotion, dairy product, fruitice preparation, confectionery, mouth and throat lozenges, coughmixtures, decongestants, antacids, oral analgesics or other medicinalproducts, chewing gum, candy (including hard candy and soft candy),fondants, toothpaste, mouthwashes, mineral water, alcoholic beverage,non-alcoholic beverage, powdered beverage, or other foodstuff comprisingthe step of adding to a cosmetic, skin care product, lip gloss, haircare product, cologne, shaving balm, after-shave lotion, dairy product,fruit ice preparation, confectionery, lozenges, cough mixtures,decongestants, antacids, oral analgesics or other medicinal product,chewing gum, candy, fondants, toothpaste, mouthwashes, mineral water,alcoholic beverage, non-alcoholic beverage, powdered beverage, or otherfoodstuff, a taste or cooling or refreshing effect augmenting, enhancingor imparting quantity and concentration of Structure I:

Structure I possesses the following flavor properties when tasted inwater at 10 ppm and at 1 ppm:

At the level of 10 ppm in water this material contributes moderatethroat and mouth cooling that lingers with some bitter notes inbackground. Cooling lasts with breath in for 30 minutes.

At the level of 1 ppm in water Structure I is clean with slight coolingup front that builds with time to moderate level. Cooling lasted for 30minutes.

Based on this flavor evaluation, it is indicative that the Structure Iof our invention are useful for augmenting, enhancing or imparting ataste or cooling or refreshing effect in or to a cosmetic, skin careproduct, lip gloss, hair care product, cologne, shaving balm,after-shave lotion, dairy product, fruit ice preparation, confectionery,mouth and throat lozenges, cough mixtures, decongestants, antacids, oralanalgesics or other medicinal products, chewing gum, candy (includinghard candy and soft candy), fondants, toothpaste, mouthwashes, mineralwater, alcoholic beverage, non-alcoholic beverage, powdered beverage, orother foodstuff as a result of adding to a cosmetic, skin care product,lip gloss, hair care product, cologne, shaving balm, after-shave lotion,dairy product, fruit ice preparation, confectionery, lozenges, coughmixtures, decongestants, antacids, oral analgesics or other medicinalproduct, chewing gum, candy, fondants, toothpaste, mouthwashes, mineralwater, alcoholic beverage, non-alcoholic beverage, powdered beverage, orother foodstuff, a taste or cooling or refreshing effect augmenting,enhancing or imparting quantity and concentration of Structure I.

As used herein the term, olfactory effective amount is understood tomean the amount of compound in flavor compositions, oral carecompositions and articles, nasal care compositions and articles, skincare compositions, hair care compositions, cosmetic compositions, andother consumable materials as defined herein, the individual componentwill contribute to its particular olfactory characteristics, but theflavor, taste and aroma effect on the overall composition will be thesum of the effects of each of the cooling and/or refreshing and/orpungent flavor and/or sense imparting, augmenting or enhancingingredients. As used herein taste effects include cooling, refreshingand pungent effects. Thus the compounds of the invention can be used toalter the taste characteristics of the flavor composition by modifyingthe taste reaction contributed by another ingredient in the composition.The amount will vary depending on many factors including otheringredients, their relative amounts and the effect that is desired.

The preferred usage level of Structure I used in products is at a levelfrom about 0.001 to about 1 weight percent (%) and more preferably 0.015to about 0.15 weight percent and most preferably about 0.04 weightpercent.

The usage levels of Structure I vary depending on the product in whichthe Structure I is employed.

Thus, with reference to the use of Structure I of our invention inalcoholic beverages, the usage level is from about 0.0005 to about 0.02weight percent, preferably from about 0.002 to about 0.0150 weightpercent and most preferably from about 0.0030 to about 0.0080 weightpercent.

With reference to the use of the Structure I of our invention innon-alcoholic beverages including carbonated beverages and fruit drinks,the non-alcoholic beverages are flavored at levels of from about 0.0001to about 0.0030 weight percent, preferably from about 0.0005 to about0.0015 weight percent.

With reference to the use of the Structure I of our invention intoothpaste, the toothpaste can be satisfactorily flavored by usingStructure I at levels of from about 0.02 to about 0.07 weight percent,more preferably from about 0.03 to about 0.06 weight percent and mostpreferable from about 0.035 up to about 0.055 weight percent.

With reference to the use of the Structure I of our invention in candyproducts including hard candy, the candy can be flavored at levels offrom about 0.05 to about 0.25 weight percent; preferably from about 0.1to about 0.2 weight percent.

With reference to the use of the Structure I of our invention in chewinggum, chewing gum usage levels are from about 0.01 to about 1 weightpercent, preferably from about 0.1 to about 0.5 weight percent and morepreferably from about 0.15 to about 0.25 weight percent.

When used in combination with other cooling compounds and compositionsone skilled in the art may modify the levels to achieve the desiredresult.

When used in combination with other cooling compounds and compositionsStructure I may be used at a level from about 0.01 to about 0.2 weightpercent.

Specifically, when used in combination with Structure I, monomenthylglutarate may be used at a level from about 0.1 to about 1 weightpercent and more preferably from about 0.25 to about 0.4 weight percent.

A preferred level of 2-isopropyl-N,2,3-trimethylbutyramid when used incombination with Structure I is from about 0.01 to about 1 weightpercent and more preferably from about 0.03 to about 0.3 weight percent.

A preferred level of menthyl acetoacetate when used in combination withStructure I is from about 0.02 to about 1.0 weight percent and morepreferably from about 0.2 to about 0.6 weight percent.

A preferred level of N-ethyl-p-menthanecarboxamide when used incombination with Structure I is from about 0.02 to about 0.5 weightpercent and more preferably from about 0.05 to about 0.2 weight percent.

The term foodstuff as used herein includes both solid and liquidingestible materials for man or animals, which materials usually do, butneed not, have nutritional value. Thus, foodstuffs include meats,gravies, soups, convenience foods, malt, alcoholic and other beverages,milk and dairy products, seafood, including fish, crustaceans, mollusksand the like, candies, vegetables, cereals, soft drinks, snacks, dog andcat foods, other veterinary products and the like.

When Structure I is used in a flavoring composition, they can becombined with conventional flavoring materials or adjuvants. Suchco-ingredients or flavor adjuvants are well known in the art for suchuse and have been extensively described in the literature. Requirementsof such adjuvant materials are: (1) that they be non-reactive withStructure I; (2) that they be organoleptically compatible with theStructure I of our invention whereby the flavor of the ultimateconsumable material to which Structure I is added is not detrimentallyaffected by the use of the adjuvant; and (3) that they be ingestibleacceptable and thus nontoxic or otherwise non-deleterious. Apart fromthese requirements, conventional materials can be used and broadlyinclude other flavor materials, vehicles, stabilizers, thickeners,surface active agents, conditioners and flavor intensifiers.

Such conventional flavoring materials include saturated fatty acids,unsaturated fatty acids and amino acids; alcohols including primary andsecondary alcohols, esters, carbonyl compounds including ketones, otherthan the menthyl half acid esters or N-alkyl alkamic acid menthyl estersof our invention and aldehydes; lactones; other cyclic organic materialsincluding benzene derivatives, acyclic compounds, heterocyclics such asfurans, pyridines, pyrazines and the like; sulfur-containing compoundsincluding thiols, sulfides, disulfides and the like; proteins; lipids,carbohydrates; so-called flavor potentiators such as monosodiumglutamate; magnesium glutamate, calcium glutamate, guanylates andinosinates; natural flavoring materials such as hydrolyzates, cocoa,vanilla and caramel; essential oils and extracts such as anise oil,clove oil and the like and artificial flavoring materials such asvanillin, ethyl vanillin and the like.

Specific preferred flavor adjuvants include but are not limited to thefollowing: anise oil; ethyl-2-methyl butyrate; vanillin; cis-3-heptenol;cis-3-hexenol; trans-2-heptenal; butyl valerate; 2,3-diethyl pyrazine;methyl cyclo-pentenolone; benzaldehyde; valerian oil;3,4-dimeth-oxyphenol; amyl acetate; amyl cinnamate; γ-butyryl lactone;furfural; trimethylpyrazine; phenyl acetic acid; isovaleraldehyde; ethylmaltol; ethyl vanillin; ethyl valerate; ethyl butyrate; cocoa extract;coffee extract; peppermint oil; spearmint oil; clove oil; anethol;cardamom oil; wintergreen oil; cinnamic aldehyde; ethyl-2-methylvalerate; γ-hexenyl lactone; 2,4-decadienal; 2,4-heptadienal; methylthiazole alcohol (4-methyl-5-β-hydroxyethyl thiazole); 2-methylbutanethiol; 4-mercapto-2-butanone; 3-mercapto-2-pentanone;1-mercapto-2-propane; benzaldehyde; furfural; furfuryl alcohol;2-mercapto propionic acid; alkyl pyrazine; methylpyrazine;2-ethyl-3-methylpyrazine; tetramethylpyrazine; polysulfides; dipropyldisulfide; methyl benzyl disulfide; alkyl thiophene; 2,3-dimethylthiophene; 5-methyl furfural; acetyl furan; 2,4-decadienal; guaiacol;phenyl acetaldehyde; β-decalactone; d-limonene; acetoin; amyl acetate;maltol; ethyl butyrate; levulinic acid; piperonal; ethyl acetate;n-octanal; n-pentanal; n-hexanal; diacetyl; monosodium glutamate;monopotassium glutamate; sulfur-containing amino acids, e.g., cysteine;hydrolyzed vegetable protein; 2-methylfuran-3-thiol;2-methyldihydrofuran-3-thiol; 2,5-dimethylfuran-3-thiol; hydrolyzed fishprotein; tetramethylpyrazine; propyl propenyl disulfide; propyl propenyltrisulfide; diallyl disulfide; diallyl trisulfide; dipropenyl disulfide;dipropenyl trisulfide; 4-methyl-2-[(methylthio)-ethyl]-1,3-dithiolane;4,5-dimethyl-2-(methylthiomethyl)-1,3-dithiolne; and4-methyl-2-(methylthiomethyl)-1,3-dithiolane. These and other flavoringredients are provided in U.S. Pat. Nos. 6,110,520 and 6,333,180.

Structure I or compositions incorporating them, as mentioned above canbe combined with one or more vehicles or carriers for adding them to theparticular product. Vehicles can be water-soluble or oil-soluble; andcan be edible or otherwise suitable materials such as ethyl alcohol,propylene glycol, water, triacetin, vegetable oil, triethyl citrate andthe like, as described supra. Carriers include materials such as gumarabic, carrageenan, xanthan gum, guar gum and the like.

Structure I prepared according to our invention can be incorporated withthe carriers by conventional means such as spray-drying, extrusion,drum-drying and the like. Such carriers can also include materials forcoacervating the menthyl half-acid ester derivatives including menthylhalf acid esters or N-alkyl alkamic acid menthyl esters of our inventionto provide encapsulated products, as set forth supra. When the carrieris an emulsion, the flavoring composition can also contain emulsifierssuch as mono- and diglycerides or fatty acids and the like. With thesecarriers or vehicles, the desired physical form of the compositions canbe prepared.

The quantity of Structure I utilized should be sufficient to impart thedesired flavor characteristic to the product, but on the other hand, theuse of an excessive amount of Structure I is not only wasteful anduneconomical, but in some instances, too large a quantity may unbalancethe flavor or other organoleptic properties of the product consumed. Thequantity used will vary depending upon the ultimate foodstuff; theamount and type of flavor initially present in the foodstuff; thefurther process or treatment steps to which the foodstuff will besubjected; regional and other preference factors; the type of storage,if any, to which the product will be subjected; and the preconsumptiontreatment such as baking, frying and so on, given to the product by theultimate consumer. Accordingly, the terminology effective amount andsufficient amount is understood in the context of the present inventionto be quantitatively adequate to alter the flavor of the foodstuff.

It will be understood that the embodiments described herein are merelyexemplary, and that one skilled in the art may make variations andmodifications without departing from the spirit and scope of theinvention. All such variations and modifications are intended to beincluded within the scope of the invention as described hereinabove.Further, all embodiments disclosed are not necessarily in thealternative, as various embodiments of the invention may be combined toprovide the desired result.

Example 1 Preparation of 4-Aminophenylacetamide

The 4-aminophenylacetamide used in this example was obtained accordingto patent literature WO 02/08247 A2 or WO 03/051909 A2. Procedure was asfollows: Methanol (200 mL) was charged to 4-aminophenylacetic acid(Aldrich) (25 g, 0.165 mol). Sulfuric acid (18 mL concentrated, 0.648mol) was added maintaining the temperature <20° C. The mixture was thenrefluxed for one hour and concentrated by distillation at atmosphericpressure until the volume of 140 mL. The mixture was then cooled to 50°C. and tert-buthyl methyl ether (300 mL) was added maintaining thetemperature above 45° C. The mixture was gradually cooled to 0-5° C. andheld at this temperature for 1 hour. The resultant crystalline productwas isolated by filtration and washed with cold methanol: tert-butylmethyl ether (20 mL: 55 mL) and cold tert-butyl methyl ether and thendried under vacuum to give methyl 4-aminophenylacetate hydrogensulfate(35.3 g, 80% yield).

Obtained compound was added to 20% w/w aqueous NaCl (65 mL). Aqueousammonia (90 mL), containing dissolved sodium chloride (15 g) was addedmaintaining the temperature 15-25° C. The mixture was then stirred for16 hours at 22° C. The mixture was cooled to 0-5° C. and held at thistemperature for one hour. The resultant crystalline product was isolatedby filtration, washed with water (2×30 mL) and dried under vacuum at 45°C. giving 13.6 g of product, 68% yield.

Preparation of(2S,5R)—N-[4-(2-Amino-2-oxoethyl)phenyl]-5-methyl-2-(propan-2-yl)cyclohexanecarboxamide

The p-Menthane-3-carboxylic acid (obtained according to publication:Desmond Cunningham, Eva T. Gallagher, David H. Grayson, Patrick J.McArdle, Christina B. Storey, Deborah J. Wilcock; J. Chem. Soc., PerkinTrans. 1, 2002, 2692-2698), (2.5 g, 13.5 mmol) was heated under refluxwith thionyl chloride (Alfa Aesar) (7 mL) for three hours. Then theexcess of thionyl chloride was distilled off in vacuo. Residue wasdissolved in CH₂Cl₂ (30 mL). This solution was added drop wise to themixture of 4-aminophenylacetamide (2.2 g, 13.5 mmol) and triethylamine(1.8 g, 17.8 mmol) at 0° C. After ten minutes the solution was allowedto warm to room temperature. After 1 hour GC showed that reaction iscompleted. CH₂Cl₂ (50 mL) was added to the reaction and this mixture waswashed by 0.1 N HCl aq, water, 0.1 N NaOH aq, by brine and dried overMgSO₄. The mixture was then filtrated and evaporated give white solidwhich was crystallized from hot ethyl acetate providing 3 g (65%)product as white solid. C₁₉H₂₈N₂O₂ (MW 316.22); ¹H NMR (500 MHz,DMSO-d6) δ: 9.79 (s, 1H), 7.51 (d, 2H, J=8.41), 7.36 (br s, 1H), 7.15(d, 2H, J=8.41 Hz), 6.82 (br s, 1H), 3.30 (s, 2H), 2.30 (t, 1H, J=11.43Hz of d, J=3.19 Hz), 1.70-1.77 (m, 2H), 1.61-1.68 (m, 2H), 1.51 (t, 1H,J=11.5 Hz, of t, J=2.8 Hz), 1.33-1.38 (brs, 1H), 1.17 (q, 1H, J=12.16Hz), 1.02 (q, 1H, J=12.7 Hz, of d, J=2.7 Hz) 0.89-0.96 (m, 1H), 0.88 (d,3H, J=6.5 Hz), 0.85 (d, 3H, J=6.9 Hz), 0.79 (d, 3H, J=6.9 Hz).

Flavor Evaluation of Structure I

At the level of 10 ppm in water this material contributes moderatethroat and mouth cooling that lingers with some bitter notes inbackground. Cooling lasts with breath in for 30 minutes.

At the level of 1 ppm in water Structure I is clean with slight coolingup front that builds with time to moderate level. Cooling lasted for 30minutes.

Example 2 Preparation of a Chewing Gum

The following gum base formulation was prepared:

TABLE I Parts by Percentage Parts by Ingredients (%) Weight (grams) GumBase, Hades-T 29.35 205.45 Maltitol Syrup 3.00 21 Sorbitol Powder 48.30338.1 Mannitol Powder 8.00 56 Glycerin 9.00 63 Sucralose 0.20 1.4Acesulfame K 0.15 1.05 Cherry Flavor 1.00 7 Total 99.00 693

The cherry flavor is commercially available from IFF. The gum base,Hades-T is commercially available from Cafosa Gum, Barcelona Spain.

Structure I by itself and in separate mixtures with monomenthylglutarate, 2-isopropyl-N,2,3-trimethylbutyramid,N-ethyl-p-menthanecarboxamide and menthyl acetoacetate at levelsdetailed in the Tables below was blended with the gum base in a Sigmamixer. The resultant chewing gum blend was then manufactured into strips1 inch in width and 0.1 inches in thickness. These strips were cut intolengths of 3 inches each. A control gum, without any coolers, was alsomanufactures into strips and this control gum exhibited a flavor withoutimparting any cooling effect.

The resulting gum blends had a substantially identical to the tasteprofile of the control gum; however the gum blends had cooling effectsas described below.

Samples were profiled by a highly trained descriptive analysis panel.The ballot consisted of the following terms: Total impact, total mint,cooling-mouth closed, cooling-breath in, nasal cooling—breath in, throatirritation, bitterness, tongue irritation, numbing. Each attribute wasrated at discrete time points including 5 secs, 30 secs, 90 secs, 3mins, 5 mins, 7 mins, 10 mins, 15 mins, 20 mins, and 30 mins.

Gum Blended with Structure I

Panelist 1 11:04 Start

11:05 Bitter, Brown, Sweet, slightly Vanilla11:06 Start to notice cooling11:08 Moderate cooling11:11 Moderate cooling in mouth and now back of the throat; nice onbreath in11:11 Continued long lasting cooling11:15 Slight cooling moving to the front of the mouth11:18 Stable cooling all over, nice level11:22 Long lasting

Panelist 2

11:04 Start, Very sweet, brown11:07 Started to notice cooling on breath and tip of the tongue11:09 Started to notice on back of throat, continued to build in therest of the mouth11:11 Cooling consistent throughout mouth, slight irritation on the backof the throat11:15 Cooling level the same11:24 Still getting a good amount of cooling12:07 Cooling is gone

Panelist 3 11:04 Start

11:07 Cooling on the back of the throat11:14 Concentrated on the back of the throat; irritating11:22 Full cooling after 20 min

Panelist 4 11:04 Start

11:07 Cooling perception begins (mild)11:09 Cooling pleasant, builds to moderate cooling on the front/tip oftongue11:11 Intensity max reached11:14 Cooling plateau, maintained. Delocalized all over mouth11:19 Remains intense11:20 Moves to throat (mild) very intense on tip of the tongue andcenter11:24 Still cooling12:00 Cooling remains12:15 Cooling diminished significantly

The following table details the panelist's results for the combinationof Structure I with monomenthyl glutarate,2-isopropyl-N,2,3-trimethylbutyramid, N-ethyl-p-menthanecarboxamide andmenthyl acetoacetate at 3 minutes, 8 minutes, 20 minutes and 30 minute,40 minute and 50 minute intervals. The amounts are listed in weightpercent.

TABLE II 2-isopropyl- monomenthyl N,2,3- N-ethyl-p- menthyl Structure Iglutarate trimethylbutyramid menthanecarboxamide acetoacetate Comments 10.036 0.12 3 minutes: clean, moderate cooling. 8 minutes: mild butpleasant cooling. 20 minutes: more cooling in throat than in mouth. Niceon breathe in. Expectorate. 30 minutes: minimal cooling in throat. 20.036 0.06 3 minutes: sharp cooling on tip of tongue and in throat. 8minutes: cooling more intense than #1 & #5. 20 minutes: pleasantcooling, still quite strong. 30 minutes: still cool. Better coolingexperienced than in #1 & #5. Expectorate 3 0.036 0.044 3 minutes:pleasant cooling. Strong on tip of tongue. Salivating. 8 minutes:moderate cooling delocalized all over tongue. 20 minutes: still coolingon tongue and roof of mouth towards the back. 30 minutes: more coolingin roof of mouth t

the back and in throat. 40 minutes: cooling in roof of mouth towards theback and in throat. Cooling on breathe in. Expectorate. 50 minutes:lingering cooling. 4 0.036 0.06 3 minutes: cooling delocalized, notintense, fairly mild. Cooling accumulating in nasal cavity. 8 minutes:coolness building. Cooling delocalized with some concentration on tip oftongue. 20 minutes: cooling intensified. Pleasant cooling especially inback of throat. 30 minutes: cooling localized in throat. Moderatecooling on center of tongue. 40 minutes: more intense than at 30minutes. Cooling on front of tongue and in throat. 50 minutes: minimalcooling. After one hour, significant residual cooling on sides of tongueand in throat.

indicates data missing or illegible when filed

1. A compound:


2. A composition selected from topical products for humans and animals,oral care products, nasal care products, and chewing gum which comprisesa product base and an effective amount of the compound of claim
 1. 3. Acomposition as claimed in claim 1 which comprises from 0.001-1.0% byweight, based on the total weight of the composition, of said coolant.4. A composition comprising a product base selected from the groupconsisting of baked goods, dairy products, fruit ices, confectioneryproducts, sugarless candies, jams, jellies, gelatins, puddings, animalfeeds, pressed confectionery tablets, hard-boiled candies, pectin-basedcandies, chewy candies, creme-centered candies, fondants, sugarlesshard-boiled candies, sugarless pectin-based candies, sugarless chewycandies, sugarless creme-centered candies, toothpastes, mouthwashes,breath fresheners, carbonated beverages, mineral waters, powderedbeverage mixes, other non-alcoholic beverages, cough drops, lozenges,cough mixtures, decongestants, anti-irritants, antacids,anti-indigestion preparations and oral analgesics, and an effectiveamount of a compound:


5. A composition as claimed in claim 4 wherein the orally ingestedproducts are selected from lozenges, cough mixtures, decongestants,anti-irritants, antacids, anti-indigestion preparations and oralanalgesics.
 6. A coolant composition which comprises an effective amountof the compound of claim 1 and at least one secondary coolant componentselected from the group consisting of menthol, menthone, monomenthylglutarate, 2-isopropyl-N,2,3-trimethylbutyramide,N-ethyl-p-menthanecarboxamide, menthyl acetoacetate and mixturesthereof.
 7. A composition as claimed in claim 4 wherein the ingestibleproduct is a foodstuff selected from the group consisting of bakedgoods, dairy products, fruit ices, confectionery products, sugarlesscandies, jams, jellies, gelatins, puddings and animal feeds.
 8. Acomposition as claimed in claim 4 wherein the topical product isselected from the group consisting of face creams, talcum powders, hairoils, shampoos, bath oils, bath salts, toilet soaps, colognes,antiperspirants, toilet water, perfume, shaving lotion, shaving cream,hair tonic, ointments and lotions.
 9. A composition as claimed in claim4 wherein the oral care product is selected from dentifrices andmouthwashes.
 10. A composition as claimed in claim 4 wherein theingestible product is cough drops.
 11. A composition as claimed in claim4 which comprises from 0.001-1.0% by weight, based on the total weightof the composition, of said coolant.
 12. A composition as claimed inclaim 4 additionally comprising at least one secondary coolant componentselected from the group consisting of menthol, menthone, monomenthylglutarate, 2-isopropyl-N,2,3-trimethylbutyramide,N-ethyl-p-menthanecarboxamide, menthyl acetoacetate and mixturesthereof.
 13. A composition as claimed in claim 4 wherein saidcomposition is selected from pressed confectionery tablets, hard boiledcandies, pectin-based candies, chewy candies, cream-centered candies,fondants, sugarless hard-boiled candies, sugarless pectin-based candies,sugarless chewy candies, sugarless cream-centered candies, animal feeds,breath fresheners, carbonated beverages, mineral waters, powderedbeverage mixes and non-alcoholic beverages.
 14. A process foraugmenting, enhancing or imparting a taste or cooling or refreshingeffect in or to a cosmetic, skin care product, lip gloss, hair careproduct, cologne, shaving balm, after-shave lotion, dairy product, fruitice preparation, confectionery, mouth and throat lozenges, coughmixtures, decongestants, antacids, oral analgesics or other medicinalproducts, chewing gum, candy, fondants, toothpaste, mouthwashes, mineralwater, alcoholic beverage, non-alcoholic beverage, powdered beverage, orother foodstuff comprising the step of adding to a cosmetic, skin careproduct, lip gloss, hair care product, cologne, shaving balm,after-shave lotion, dairy product, fruit ice preparation, confectionery,lozenges, cough mixtures, decongestants, antacids, oral analgesics orother medicinal product, chewing gum, candy, fondants, toothpaste,mouthwashes, mineral water, alcoholic beverage, non-alcoholic beverage,powdered beverage, or other foodstuff, a taste or cooling or refreshingeffect augmenting, enhancing or imparting quantity and concentration ofStructure I:


15. The process of claim 14 additionally comprising at least onesecondary coolant component selected from the group consisting ofmenthol, menthone, monomenthyl glutarate,2-isopropyl-N,2,3-trimethylbutyramide, N-ethyl-p-menthanecarboxamide,menthyl acetoacetate and mixtures thereof.
 16. A chewing gum compositioncomprising a gum base, a sweetener and N-substituted-p-menthanecarboxamide of the following Structure I:


17. The chewing gum composition of claim 16 additionally comprising atleast one secondary coolant component selected from the group consistingof menthol, menthone, monomenthyl glutarate,2-isopropyl-N,2,3-trimethylbutyramide, N-ethyl-p-menthanecarboxamide,menthyl acetoacetate and mixtures thereof.